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Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic acid for prevention of radiation-induced liver toxicity.

Seidensticker M, Seidensticker R, Damm R, Mohnike K, Pech M, Sangro B, Hass P, Wust P, Kropf S, Gademann G, Ricke J - PLoS ONE (2014)

Bottom Line: Targeted radiotherapy of liver malignancies has found to be effective in selected patients.We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).No significant differences between the groups were observed at the 12-week follow-up.

View Article: PubMed Central - PubMed

Affiliation: Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; International School of Image-Guided Interventions, Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.

ABSTRACT

Background/aim: Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).

Methods and materials: Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data.

Results: Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up.

Conclusions: The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1-8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI.

Trial registration: EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304.

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Related in: MedlinePlus

CONSORT-diagram.*Exclusion criterion age was initially disregarded by error in this patient (aged 82). **Exclusion criterion prior radiotherapy was initially disregarded by error in this patient (prior radiotherapy was performed 2 years earlier with location in the contralateral liver lobe).
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pone-0112731-g002: CONSORT-diagram.*Exclusion criterion age was initially disregarded by error in this patient (aged 82). **Exclusion criterion prior radiotherapy was initially disregarded by error in this patient (prior radiotherapy was performed 2 years earlier with location in the contralateral liver lobe).

Mentions: Consecutive patients (18–80 years) with liver metastases from mCRC, who were scheduled for local ablation with computed-tomography (CT)/MRI-guided BT between 2009 and 2012, were screened (Figure 2). (BT is the local standard ablative treatment in patients ineligible for surgical or all other appropriate intervention).


Prospective randomized trial of enoxaparin, pentoxifylline and ursodeoxycholic acid for prevention of radiation-induced liver toxicity.

Seidensticker M, Seidensticker R, Damm R, Mohnike K, Pech M, Sangro B, Hass P, Wust P, Kropf S, Gademann G, Ricke J - PLoS ONE (2014)

CONSORT-diagram.*Exclusion criterion age was initially disregarded by error in this patient (aged 82). **Exclusion criterion prior radiotherapy was initially disregarded by error in this patient (prior radiotherapy was performed 2 years earlier with location in the contralateral liver lobe).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231047&req=5

pone-0112731-g002: CONSORT-diagram.*Exclusion criterion age was initially disregarded by error in this patient (aged 82). **Exclusion criterion prior radiotherapy was initially disregarded by error in this patient (prior radiotherapy was performed 2 years earlier with location in the contralateral liver lobe).
Mentions: Consecutive patients (18–80 years) with liver metastases from mCRC, who were scheduled for local ablation with computed-tomography (CT)/MRI-guided BT between 2009 and 2012, were screened (Figure 2). (BT is the local standard ablative treatment in patients ineligible for surgical or all other appropriate intervention).

Bottom Line: Targeted radiotherapy of liver malignancies has found to be effective in selected patients.We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).No significant differences between the groups were observed at the 12-week follow-up.

View Article: PubMed Central - PubMed

Affiliation: Universitätsklinik Magdeburg, Klinik für Radiologie und Nuklearmedizin, Magdeburg, Germany; International School of Image-Guided Interventions, Deutsche Akademie für Mikrotherapie, Magdeburg, Germany.

ABSTRACT

Background/aim: Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI).

Methods and materials: Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data.

Results: Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up.

Conclusions: The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1-8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI.

Trial registration: EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304.

Show MeSH
Related in: MedlinePlus